The overall goal of this HIVRAD Program is to develop a second generation HIV-1 vaccine based on recombinant adeno-associated virus (rAAV) vectors. The proposed research in this application builds on our experience with a first generation rAAV/HIV vaccine that is now being tested in Phase I human trials. Although the first generation vaccine is a promising candidate, we believe that substantial room for improvement remains. Based on our preliminary data, we have developed a series of hypothesis driven experiments to achieve this goal. We will enhance antigen-specific T cell responses to the vaccine by (i) significantly augmenting vaccine gene delivery and (ii) directly engaging and modifying host immune responses.